ELR-CXC chemokine antagonism is neuroprotective in a rat model of ischemic stroke

Neuroscience Letters
Barry J ConnellTarek M Saleh

Abstract

Inflammation-related cerebral damage mediated by infiltrating neutrophils following reperfusion plays a role in reperfusion-induced brain damage subsequent to a stroke event. The ELR-CXC family of chemokines are CXCR1 and CXCR2 agonists that are known to drive neutrophil migration and activation. The present study demonstrated the benefit of anti-inflammatory therapy in the treatment of ischemic stroke with the administration of the competitive ELR-CXC chemokine antagonist, CXCL8(3-72)K11R/G31P (G31P). Male Sprague-Dawley rats were anaesthetized, and the middle cerebral artery (MCA) was occluded for 30 min followed by 5.5 h of reperfusion. Pretreatment with G31P resulted in a significant, dose-dependent (approximately 61-72%) decrease in infarct volumes compared to vehicle-treated animals, but neuroprotection was also observed when G31P (0.5 mg/kg) was administered 1 or 3 h following the start of reperfusion. The neuroprotection observed following the administration of this competitive CXCR1/CXCR2 antagonist may present therapeutic opportunities for addressing reperfusion-induced inflammatory damage in patients presenting with transient ischemic episodes.

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Citations

Jun 21, 2017·Neurochemistry International·Chen ChenNai-Hong Chen
Nov 5, 2017·Biochemical Society Transactions·Bernd Gesslbauer, Valery Bochkov
Sep 21, 2018·Experimental and Therapeutic Medicine·Wei ZhangShumin Li
Apr 20, 2019·Frontiers in Physiology·Tracylyn R YellowhairLauren L Jantzie
Mar 21, 2020·Frontiers in Molecular Neuroscience·Liquan WuLijuan Gu

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